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  • 201.
    Olofsson, Jörgen
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Developing and evaluating dose calculation models for verification of advanced radiotherapy2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A prerequisite for modern radiotherapy is the ability to accurately determine the absorbed dose (D) that is given to the patient. The subject of this thesis has been to develop and evaluate efficient dose calculation models for high-energy photon beams delivered by linear accelerators. Even though the considered calculation models are general, the work has been focused on quality assurance (QA) tools used to independently verify the dose for individual treatment plans. The purpose of this verification is to guarantee patient safety and to improve the treatment outcome. Furthermore, a vital part of this work has been to explore the prospect of estimating the dose calculation uncertainties associated with individual treatment setups. A discussion on how such uncertainty estimations can facilitate improved clinical QA procedures by providing appropriate action levels has also been included within the scope of this thesis.

    In order to enable efficient modelling of the physical phenomena that are involved in dose output calculations it is convenient to divide them into two main categories; the first one dealing with the radiation exiting the accelerator’s treatment head and a second one associated with the subsequent energy deposition processes. A multi-source model describing the distribution of energy fluence emitted from the treatment head per delivered monitor unit (MU) is presented and evaluated through comparisons with measurements in multiple photon beams and collimator settings. The calculations show close agreement with the extensive set of experimental data, generally within +/-1% of corresponding measurements.

    The energy (dose) deposition in the irradiated object has been modelled through a photon pencil kernel solely based on a beam quality index (TPR20,10). This model was evaluated in a similar manner as the multi-source model at three different treatment depths. A separate study was focused on the specific difficulties associated with dose calculations in points located at a distance from the central beam axis. Despite the minimal input data required to characterize individual photon beams, the accuracy proved to be very good when comparing the calculated results with experimental data.

    The evaluated calculation models were finally used to analyse how well the lateral dose distributions from typical megavoltage photon beams are optimized with respect to the resulting beam flatness characteristics. The results did not reveal any obvious reasons why different manufacturers should provide different lateral dose distributions. Furthermore, the performed lateral optimizations indicate that there is room for improved flatness performance for the investigated linear accelerators.

  • 202.
    Olofsson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Energy and intensity modulated radiation therapy with electrons2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In recent years intensity modulated radiation therapy with photons (xIMRT) has gained attention due to its ability to reduce the dose in the tissues close to the tumour volume. However, this technique also results in a large low dose volume. Electron IMRT (eIMRT) has the potential to reduce the integral dose to the patient due to the dose fall off in the electron depth dose curves. This dose fall off makes it possible to modulate the dose distribution in the direction of the beam by selecting appropriate electron energies. The use of a computer based energy selection method was examined in combination with the IMRT technique to optimise the electron dose distribution. It is clearly illustrated that the energy optimisation procedure reduces the dose to lung and heart in a breast cancer treatment.

    To shape the multiple electron subfields (beamlets) that are used in eIMRT, an electron multi leaf collimator (eMLC) is needed. However, photons produced in a conventional electron treatment head could penetrate such an added eMLC, thus producing an undesirable dose contribution. The leakage levels normally achieved are acceptable for standard single electron field treatments but could become unacceptably high in eIMRT treatments where a lot of small subfields are combined. To limit this photon contribution, the photon MLC (xMLC) was used to shield off large parts of the photon leakage.

    The effect of this xMLC shielding on the reduction of photon leakage, the electron beam penumbras, and electron output (dose level), was studied using Monte Carlo methods for different electron treatment head designs. The use of helium as a mean to reduce the electron scatter in the treatment head, and thus the perturbating effect of the xMLC on electron beam penumbra and output, was also investigated.

    This thesis shows that the effect of the xMLC shielding on the electron beam penumbra and output can be made negligible while still obtaining a significantly reduced x-ray leakage dose contribution. The result is a large gain in radiation protection of the patient and a better dynamic range for the eIMRT dose optimisation. For this optimisation a computer based electron energy selection method was developed and tested on two clinical cases.

  • 203. Olsson, C.
    et al.
    Nyholm, T.
    Wieslander, E.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Valdman, A.
    Initial Experience with Introducing National Swedish Guidelines for CT- and MRI-based Delineation of Organs at Risk in Radiotherapy: The STRONG Project2019In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 105, no 1, p. E620-E620Article in journal (Refereed)
  • 204.
    Parkkinen, Jyrki
    et al.
    Departmen of Anatomy,University of Kuopio, Kuopio, Finland.
    Paukkonen, Kari
    Departmen of Anatomy, University of Kuopio, Kuopio, Finland.
    Pesonen, Erkki
    Departmen of Computer Science and Applied Mathematics, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Departmen of Anatomy, University of Kuopio, Kuopio, Finland.
    Markkanen, Seppo
    Departmen of Anatomy, University of Kuopio, Kuopio, Finland.
    Helminen, Heikki
    Departmen of Anatomy, University of Kuopio, Kuopio, Finland.
    Tammi, Markku
    Departmen of Anatomy, University of Kuopio, Kuopio, Finland.
    Quantitation of autoradiographic grains in different zones of articular cartilage with image analyzer.1990In: Histochemistry, ISSN 0301-5564, Vol. 93, no 3, p. 241-245, article id 2312351Article in journal (Refereed)
    Abstract [en]

    A novel method is introduced for the estimation of grain numbers in autoradiographic sections of articular cartilage with an image analyzer. It is based on separation of grains from the underlying structures by gray level thresholding and determination of the percentage of total area occupied by grains in a relatively large measuring field. The mean grain size is used as a reference to calculate grain numbers per cell profile and per unit area of tissue in various zones of bovine articular cartilage labelled with 35S-sulphate in tissue culture. The results demonstrate considerable zonal differences as well as site related topographic variation in the rate of 35S-sulphate incorporation. The largest site-related variation in the grain counts was observed in the superficial zone, suggesting a delicate control of proteoglycan synthesis in this zone.

  • 205. Persson, Emilia
    et al.
    Gustafsson, Christian
    Nordström, Fredrik
    Sohlin, Maja
    Gunnlaugsson, Adalsteinn
    Petruson, Karin
    Rintelä, Niina
    Hed, Kristoffer
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Olsson, Lars E.
    Siversson, Carl
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    MR-OPERA: a multicenter/multivendor validation of magnetic resonance imaging–only prostate treatment planning using synthetic computed tomography images2017In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 99, no 3, p. 692-700Article in journal (Refereed)
    Abstract [en]

    Purpose: To validate the dosimetric accuracy and clinical robustness of a commercially available software for magnetic resonance (MR) to synthetic computed tomography (sCT) conversion, in an MR imaging–only workflow for 170 prostate cancer patients.

    Methods and Materials: The 4 participating centers had MriPlanner (Spectronic Medical), an atlas-based sCT generation software, installed as a cloud-based service. A T2-weighted MR sequence, covering the body contour, was added to the clinical protocol. The MR images were sent from the MR scanner workstation to the MriPlanner platform. The sCT was automatically returned to the treatment planning system. Four MR scanners and 2 magnetic field strengths were included in the study. For each patient, a CT-treatment plan was created and approved according to clinical practice. The sCT was rigidly registered to the CT, and the clinical treatment plan was recalculated on the sCT. The dose distributions from the CT plan and the sCT plan were compared according to a set of dose-volume histogram parameters and gamma evaluation. Treatment techniques included volumetric modulated arc therapy, intensity modulated radiation therapy, and conventional treatment using 2 treatment planning systems and different dose calculation algorithms.

    Results: The overall (multicenter/multivendor) mean dose differences between sCT and CT dose distributions were below 0.3% for all evaluated organs and targets. Gamma evaluation showed a mean pass rate of 99.12% (0.63%, 1 SD) in the complete body volume and 99.97% (0.13%, 1 SD) in the planning target volume using a 2%/2-mm global gamma criteria.

    Conclusions: Results of the study show that the sCT conversion method can be used clinically, with minimal differences between sCT and CT dose distributions for target and relevant organs at risk. The small differences seen are consistent between centers, indicating that an MR imaging–only workflow using MriPlanner is robust for a variety of field strengths, vendors, and treatment techniques.

  • 206. Persson, Mats
    et al.
    Bujila, Robert
    Nowik, Patrik
    Andersson, Henrik
    Kull, Love
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bornefalk, Hans
    Danielsson, Mats
    Upper limits of the photon fluence rate on CT detectors: case study on a commercial scanner2016In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 43, no 7, p. 4398-4411Article in journal (Refereed)
    Abstract [en]

    Purpose: The highest photon fluence rate that a computed tomography (CT) detector must be able to measure is an important parameter. The authors calculate the maximum transmitted fluence rate in a commercial CT scanner as a function of patient size for standard head, chest, and abdomen protocols.

    Methods: The authors scanned an anthropomorphic phantom (Kyoto Kagaku PBU-60) with the reference CT protocols provided by AAPM on a GE LightSpeed VCT scanner and noted the tube current applied with the tube current modulation (TCM) system. By rescaling this tube current using published measurements on the tube current modulation of a GE scanner [N. Keat, “CT scanner automatic exposure control systems,” MHRA Evaluation Report 05016, ImPACT, London, UK, 2005], the authors could estimate the tube current that these protocols would have resulted in for other patient sizes. An ECG gated chest protocol was also simulated. Using measured dose rate profiles along the bowtie filters, the authors simulated imaging of anonymized patient images with a range of sizes on a GE VCT scanner and calculated the maximum transmitted fluence rate. In addition, the 99th and the 95th percentiles of the transmitted fluence rate distribution behind the patient are calculated and the effect of omitting projection lines passing just below the skin line is investigated.

    Results: The highest transmitted fluence rates on the detector for the AAPM reference protocols with centered patients are found for head images and for intermediate-sized chest images, both with a maximum of 3.4 ⋅ 108 mm−2 s−1, at 949 mm distance from the source. Miscentering the head by 50 mm downward increases the maximum transmitted fluence rate to 5.7 ⋅ 108 mm−2 s−1. The ECG gated chest protocol gives fluence rates up to 2.3 ⋅ 108 − 3.6 ⋅ 108 mm−2 s−1 depending on miscentering.

    Conclusions: The fluence rate on a CT detector reaches 3 ⋅ 108 − 6 ⋅ 108 mm−2 s−1 in standard imaging protocols, with the highest rates occurring for ECG gated chest and miscentered head scans. These results will be useful to developers of CT detectors, in particular photon counting detectors.

  • 207.
    Persson, My
    Umeå University, Faculty of Medicine, Department of Nursing.
    "Den värsta tiden i mitt liv...": En litteraturstudie om kvinnors upplevelser i samband med trippeldiagnostik vid misstänkt bröstcancer2014Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Breast cancer is one of the most common cancer diseases for women. With the help of regular participation of mammography screening there is a high rate of finding breast cancer in an early state. Another way to find breast cancer is when women feel something abnormal in their breast, for example a lump. To diagnose breast cancer you use examinations such as mammography and ultrasound with possible biopsy sample, these examinations are called triple diagnosis. Through the experience of suspecting breast cancer, during the breast examinations until the moment women get their diagnosis different feelings arise. Aim: The aim of this literature study was to elucidate women's lived experience during the triple diagnosis of suspected breast cancer disease. Method: Eight scientific articles were found through database searching on the databases CINAHL and Scopus. Manual search were also made. The search and analyzing were made to fulfill the purpose of this literature study. Results: The eight analyzed articles were summed up to three categories and six subcategories. These categories were “Communication at the time of the examination”, “Examination-experience” and “In the process of waiting for results”. Conclusions: Women who suspect having breast cancer experienced the feelings of fear, worry and anxiety throughout the whole process until diagnosis. The literature study “The worst time of my life…” gives X-ray nurses an insight of women‘s lived experiences of the examinations through their time of suspected breast cancer. With this insight x-ray nurses learn to inform, examine and meet their patients professionally and with respect.

  • 208.
    Peters, Bjorn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Andersson, Yvonne
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mölne, Johan
    Jensen, Gert
    Dahlberg, Per
    Holm-Gunnarsson, Inger
    Ekberg, Jana
    Bjurström, Karl
    Haux, Stina-Britta
    Hadimeri, Henrik
    A study of clinical complications and risk factors in 1001 native and transplant kidney biopsies in Sweden2014In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 55, no 7, p. 890-896Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, native and transplant kidney biopsies are usually performed in major renal medical centers. Purpose: To clarify risk factors in native and transplant kidney biopsies to improve patient safety. Material and Methods: A total of 1001 biopsies (in 352 women and 565 men) were included. The median age was 54 years (range, 16-90 years). Data were derived from 826 native kidney biopsies (640 prospective and 186 retrospective) and 175 transplant kidney biopsies (170 prospective and 5 retrospective). Various factors and complications were registered while performing native and transplant kidney biopsies, focusing on major (e. g. blood transfusions, invasive procedures) and minor complications. The prospective protocol was used at six centers and at one center data were obtained retrospectively. Results: Women were at greater risk of overall complications than men (12.2% vs. 6.5%; P = 0.003; odds ratio [OR], 2.0; confidence interval [CI], 1.3-3.1) as well as of major complications (9.6% vs. 4.5%; P = 0.002; OR, 2.2, CI 1.3-3.7). Major complications occurred more commonly after biopsies from the right kidney, in women than in men (10.8% vs. 3.1%; P = 0.005; OR, 3.7; CI, 1.5-9.5), and in patients with lower BMI (25.5 vs. 27.3, P = 0.016) and of younger age (45 years vs. 52.5 years; P = 0.001). Lower mean arterial pressure in transplant kidney biopsies indicated a risk of major complications (90 mmHg vs. 98 mmHg; P = 0.039). Factors such as needle size, number of passes, serum creatinine, and eGFR did not influence complication rates. Conclusion: The present findings motivate greater attention being paid to the risk of major side-effects after right-side biopsies from women's kidneys, as well as after biopsies from younger patients and patients with lower BMI.

  • 209. Pixberg, Caroline
    et al.
    Koch, Raphael
    Eich, Hans Theodor
    Martinsson, Ulla
    Kristensen, Ingrid
    Matuschek, Christiane
    Kortmann, Rolf-Dieter
    Pohl, Fabian
    Elsayad, Khaled
    Christiansen, Hans
    Willich, Normann
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Steinmann, Diana
    Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration2016In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 94, no 4, p. 792-799Article in journal (Refereed)
    Abstract [en]

    Purpose: In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae.

    Materials and Methods: Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria.

    Results: As of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P <=.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity.

    Conclusions: Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute toxicity grade. Age seems to influence the time until maximal late toxicity but not the development of acute toxicity.

  • 210.
    Puhakka, Pia
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Ylärinne, Janne
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Saarakkala, Simo
    Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu, Finland.
    Tiitu, Virpi
    School of Medicine, Institute of Biomedicine, Anatomy, University of Eastern Finland, Kuopio, Finland.
    Kröger, Heikki
    Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland.
    Tuomas, Virén
    Cancer Center, Kuopio University Hospital, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Dependence of light attenuation and backscattering on collagen concentration and chondrocyte density in agarose scaffolds2014In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 59, no 21, p. 6537-6548Article in journal (Refereed)
    Abstract [en]

    Optical coherence tomography (OCT) has been applied for high resolution imaging of articular cartilage. However, the contribution of individual structural elements of cartilage on OCT signal has not been thoroughly studied. We hypothesize that both collagen and chondrocytes, essential structural components of cartilage, act as important light scatterers and that variation in their concentrations can be detected by OCT through changes in backscattering and attenuation. To evaluate this hypothesis, we established a controlled model system using agarose scaffolds embedded with variable collagen concentrations and chondrocyte densities. Using OCT, we measured the backscattering coefficient (µb) and total attenuation coefficient (µt) in these scaffolds. Along our hypothesis, light backscattering and attenuation in agarose were dependent on collagen concentration and chondrocyte density. Significant correlations were found between µt and chondrocyte density (ρ = 0.853, p < 0.001) and between µt and collagen concentration (ρ = 0.694, p < 0.001). µb correlated significantly with chondrocyte density (ρ = 0.504, p < 0.001) but not with collagen concentration (ρ = 0.103, p = 0.422) of the scaffold. Thus, quantitation of light backscattering and, especially, attenuation could be valuable when evaluating the integrity of soft tissues, such as articular cartilage with OCT.

  • 211.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lundkvist, Bo
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus2013In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, no 7, p. 735-741Article in journal (Refereed)
    Abstract [en]

    Background: It is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH.

    Methods: 51 INPH patients were investigated with lumbar CSF dynamic investigations preoperatively and 5 months after shunt surgery. During the investigation, ICP was measured at baseline, and then a CSF sample was removed, resulting in pressure reduction. After this, ICP was regulated with an automated infusion protocol, with a maximum increase of 24 mm Hg above baseline. The pulsatility curve was thus determined in a wide range of ICP values. Gait improvement was defined as a gait speed increase >= 0.1 m/s.

    Results: The pulsatility curve was unaltered by shunting. Baseline ICP and amplitude were reduced (-3.0 +/- 2.9 mm Hg; -1.1 +/- 1.5 mm Hg; p < 0.05, n = 51). Amplitude reduction was larger for gait improvers (-1.2 +/- 1.6 mm Hg, n = 42) than non-improvers (-0.2 +/- 0.5 mm Hg, n = 9) (p < 0.05) although mean ICP reduction did not differ.

    Conclusions: The pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.

  • 212. Rasmusson, E.
    et al.
    Gunnlaugsson, A.
    Wieslander, E.
    Hoglund, P.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Kjellen, E.
    Nilsson, P.
    Erectile Dysfunction and Absorbed Dose to Penile Base Structures in a Randomized Trial Comparing Ultrahypofractionated and Conventionally Fractionated Radiotherapy for Prostate Cancer2019In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 105, no 1, p. S133-S134Article in journal (Refereed)
  • 213.
    Rieckmann, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Johnson, Keith A.
    Sperling, Reisa A.
    Buckner, Randy L.
    Hedden, Trey
    Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging2018In: Proceedings of the National Academy of Sciences, Vol. 115, no 40, p. 10160-10165Article in journal (Refereed)
    Abstract [en]

    Age-related changes in striatel function are potentially important for predicting declining memory performance over the adult life span. Here, we used fMRI to measure functional connectivity of caudate subfields with large-scale association networks and positron emission tomography to measure striatal dopamine transporter (DAT) density in 51 older adults (age 65-86 years) who received annual cognitive testing for up to 7 years (mean = 5.59, range 2-7 years). Analyses showed that cortical-caudate functional connectivity was less differentiated in older compared with younger adults (n = 63, age 18-32 years). Unlike in younger adults, the central lateral caudate was less strongly coupled with the frontal parietal control network in older adults. Older adults also showed less "decoupling" of the caudate from other networks, including areas of the default network (DN) and the hippocampal complex. Contrary to expectations, less decoupling between caudate and the DN was not associated with an age-related reduction of striatal DAT, suggesting that neurobiological changes in the cortex may drive dedifferentiation of cortical-caudate connectivity. Reduction of specificity in functional coupling between caudate and regions of the DN predicted memory decline over subsequent years at older ages. The age-related reduction in striatal DAT density also predicted memory decline, suggesting that a relation between striatal functions and memory decline in aging is multifaceted. Collectively, the study provides evidence highlighting the association of age-related differences in striatal function to memory decline in normal aging.

  • 214.
    Rottke, Dennis
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Digital Diagnostic Center, Freiburg im Breisgau, Germany.
    Dreger, Julia
    Sawada, Kunihiko
    Honda, Kazuya
    Schulze, Dirk
    Comparison of manual and dose reduction modes of a MORITA R100 CBCT2019In: Dento-Maxillo-Facial Radiology, ISSN 0250-832X, E-ISSN 1476-542X, Vol. 48, no 2, article id 20180009Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:: To compare effective dose differences when acquiring (1) dose reduction mode and (2) manual mode in a MORITA R100 CBCT.

    METHODS:: 24 exposure protocols with different technique factors were performed in both the dose reduction mode and the manual mode in a Veraviewepocs 3D R100 cone beam CT device. 48 TLD were placed in a RANDO head phantom at 24 different sites. Effective doses were calculated according to the formalism published in the 103rd ICRP report.

    RESULTS:: Effective doses for the dose reduction mode protocols ranged from 14 to 156 µSv [mean = 57 µSv, standard deviation (SD) = 37 µSv], whereas effective doses for the manual mode protocols ranged from 22 to 267 µSv (mean = 94 µSv, SD = 65 µSv). Thus, across all protocols, the dose reduction mode leads to a drop of the effective dose by 38 % (SD = 6 %).

    CONCLUSIONS:: The estimated effective doses are significantly lower if dose reduction protocols are acquired.

  • 215.
    Rottke, Dennis
    et al.
    Department of Craniomaxillofacial Surgery, Plastic Surgery, Faculty of Health, University Witten/Herdecke, Hospital Dortmund, Witten/Herdecke, Germany; Digital Diagnostic Center Ltd, Freiburg im Breisgau, Germany.
    Gohlke, Lisa
    Schrödel, Robert
    Hassfeld, Stefan
    Schulze, Dirk
    Operator safety during the acquisition of intraoral images with a handheld and portable X-ray device2018In: Dento-Maxillo-Facial Radiology, ISSN 0250-832X, E-ISSN 1476-542X, Vol. 47, no 3, article id 20160410Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The present study aims at investigating different radiation protection issues and dose values while acquiring intraoral images with a handheld X-ray device.

    METHODS: An Aribex NOMAD Pro 2™, a RANDO® male head phantom, a consistency testing body, a PTW NOMEX® Multimeter, and a PTW Farmer® Ionization Chamber Type 30,010 were used to investigate: (1) dose area products; (2) the expansion of the control area (CA); (3) the scattering pattern and (4) the potential risk for operators of the X-ray device.

    RESULTS: Dose area products at different exposure times were distributed linearly with a high correlation factor (>0.9). At 4000 simulated exposures, the greatest extent of the CA was 42 cm (mean = 16.7 cm, SD = 10.8 cm). The highest occurrence of scattering radiation resulted between the RANDO® phantom and the X-ray device. No scattered radiation was measured at the dorsal part of the phantom or on the operator site of a virtual vertical plane through the focal spot of the X-ray.

    CONCLUSIONS: Through this study, we could demonstrate that the application of an Aribex NOMAD Pro 2 device for intraoral imaging does not increase the risk for the operator if the device is controlled according to the manufacturer's specifications. Furthermore, we were able to show that the CA was significantly smaller than specified by European and other international radiation protection standards.

  • 216.
    Rönnqvist, Louise
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Domellöf, Erik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Johansson, Anna-Maria
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy. Umeå University, Faculty of Social Sciences, Department of Psychology.
    Faroogi, Aijaz
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Effects of twin-births on IQ, handedness, and brain volumes in 8-years-old preterm born twins and matched singletons: a pilot study2016In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 58, no S6, p. 57-Article in journal (Refereed)
    Abstract [en]

    Background: Children born preterm have a high prevalence of long-term cognitive and behavioral disturbances. Still, studies of how preterm-twin-births may effect brain maturation and thus, contribute to long-term effects on brain-behavioral development and functions are rare.

    Aim: To investigate whether brain volumes differ between twin (TPB) and singleton preterm born (SPB) and full-term born children (FTB) and associate to long-term cognitive and behavioral outcomes as well as to gestational age (GA), birth weight (BW) and head circumference (BHC) at birth.

    Method: A sample of 22 twin born preterm (Mean GA=32.1, BW=1781), 23 matched singletons preterm (Mean GA=31.8, BW=1751), and 22 full-term singletons were included. All children were investigated by means of their cognition functions (WISC-IV), handedness performance index and brain volumes (3 Tesla MRI) at early school ages (M=7.8y) in 40 children (9 TPB, 10 SPB, 21 FTB).

    Results: The FTB-children performed better than both TPB and SPB on cognitive performance, and showed higher IQ. Brain volumes, especially Gray matter were stronger associated with IQ in the twins. Furthermore it was found that the SPB singletons had smaller Total Brain volume and less Grey Matter than FTB. The twins showed a higher prevalence of non-right handedness associated to GA, than both SPB and FTB. Independently of birth status, GA, BW and BHC were found to correlate positively with IQ, Total Brain volume, and Gray-and White matter volumes.

    Conclusion: Discordant handedness in TPB children and associations to lower GA indicate effect of twin-births on early functional laterality. The overall associations found between low GA/BW and smaller BHC at birth in preterm born and associations with lower IQ and smaller brain volumes at 8-y indicate that a very preterm birth are a higher predictor for long-term effects on brain development and cognitive performance than twin-birth per se.

  • 217.
    Rönnqvist, Louise
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Domellöf, Erik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Johansson, Anna-Maria
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lindqvist, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Long term effects of preterm births: associations between upper-limb kinematics, brain volumes and cognitive functions2014In: Congress Programme. 1st Clinical Movement Analysis Word Conference, 2014, p. 310-310Conference paper (Refereed)
    Abstract [en]

    INTRODUCTION and AIM

    Studies of long-term outcomes linked to a preterm birth have generally found increasing amount of neurodevelopmental and cognitive disabilities and delays. Still, few have addressed the upper-limb performance by means of kinematic outcomes in associations with cognitive functions and brain volumes. Thus, the main aim of this study was to investigate such possible relationships within school age preterm born children and in relation to their gestational age (GA) at birth.

    PATIENTS/MATERIALS and METHODS

    The present study is part of a longitudinal, ongoing multidisciplinary project with the goal to discover possible long-term effects of a preterm birth. In this sub-study 7-9-years-old children born preterm (PT) without early sign of neuropathology (N= 24, Mean GW=32, range 22-35) in comparison to age matched term born children (N=31) was included. Kinematics was measured by ProReflex, 3D-registration during task specific, bi- and uni-manual upper-limb movement performance. Additionally, functional brain volumes were investigated by 3-Tesla (T) magnetic resonance imaging (MRI) and cognitive functions by the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV).

    RESULTS

    Our preliminary results show significant poorer upper-limb kinematics with more segmented and longer movement paths in the PT-born children in comparison to the term born, this was particular evident for thus children born very- and extremely PT (<32 GA). In agreement with this finding, a decreased total brain volume and regional gray matter reduction were significantly correlated with more segmented arm and head movement trajectories, and with poorer general IQ outcomes, as well as with lower gestational ages.

    DISCUSSION and CONCLUSIONS

    The findings from the present study show that a preterm birth, and especially a very- and extremely preterm birth, may cause long-term effects on the development of neurophysiology mechanism involved in the goal-directed upper-limb movements. Additionally, it shows that the development of the neuro-motor mechanisms also are associated with both cognitive functions and the general brain development. Thus, indicating that a very preterm birth seemingly still give neuro-developmental related problems when at school age.

  • 218.
    Saarakkala, Simo
    et al.
    Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Laasanen, Mikko
    Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Törrönen, Kari
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lappalainen, Reijo
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Applied Physics, University of Kuopio, Kuopio, Finland.
    Ultrasound indentation of normal and spontaneously degenerated bovine articular cartilage.2003In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 11, no 9, p. 697-705, article id 12954241Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We have previously developed a handheld ultrasound indentation instrument for the diagnosis of cartilage degeneration. The instrument has been demonstrated to be capable of quantifying mechanical and acoustic properties of enzymatically degraded and normal bovine articular cartilage in vitro and in situ. The aim of this study was to investigate the sensitivity of the instrument to distinguish between normal and spontaneously degenerated (e.g., in osteoarthrosis) articular cartilage in vitro.

    DESIGN: Thirty articular cartilage samples were prepared from the bovine lateral patellae: 19 patellae with different degenerative stages and 11 patellae with visually normal appearance. Cartilage thickness, stiffness (dynamic modulus) and ultrasound reflection from the cartilage surface were measured with the handheld instrument. Subsequently, biomechanical, histological and biochemical reference measurements were conducted.

    RESULTS: Reproducibility of the measurements with the ultrasound indentation instrument was good. Standardized coefficient of variation was < or =6.1% for thickness, dynamic modulus and reflection coefficient. Linear correlation between the dynamic modulus, measured with the ultrasound indentation instrument, and the reference dynamic modulus was high (r=0.993, n=30, P<0.05). Ultrasound reflection coefficient, as determined from the cartilage surface, showed high linear correlations (typically r(2)>0.64, n=30, P<0.05) with the cartilage composition and histological or mechanical properties. The instrument was superior compared to visual evaluation in detecting tissue degeneration.

    CONCLUSION: This study indicates that the ultrasound indentation technique and instrument may significantly improve the early diagnosis of cartilage degeneration. The results revealed that visual evaluation is insensitive for estimating the structural and mechanical properties of articular cartilage at the initial stages of degeneration.

  • 219.
    Sahlman, Janne
    et al.
    Seinäjoki Central Hospital, Seinäjoki, Finland.
    Pitkänen, Marja
    University Hospital of Kuopio, Kuopio, Finland.
    Prockop, Darwin
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Arita, Machiko
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Li, Shi-Wu
    Center fo Gene Therapy, MCP Hahnemann University School of Medicine, Philadelphia, Pensylvania, USA.
    Helminen, Heikki
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Långsjö, Teemu
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Puustjärvi, Kaija
    Helsinki University Hospital, Helsinki, Finland.
    Lammi, Mikko
    Department of Anatomy, University of Kuopio, Kuopio, Finland.
    A human COL2A1 gene with an Arg519Cys mutation causes osteochondrodysplasia in transgenic mice.2004In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 50, no 10, p. 3153-3160, article id 15476249Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: An arginine-to-cysteine substitution at position 519 of the COL2A1 gene causes early generalized osteoarthritis with mild chondrodysplasia in humans. In this study, a human COL2A1 gene with the same mutation was introduced into a murine genome having 1 or no alleles of the murine Col2a1 gene, and the skeletal phenotypes of the transgenic mice were compared with those of control mice.

    METHODS: Mice with 1 allele of the normal murine Col2a1 gene and 1 allele of the mutated human COL2A1 gene (n = 10), those with no murine Col2a1 gene and 2 alleles of the mutated human COL2A1 gene (n = 13), those with no murine Col2a1 gene and only 1 allele of the mutated COL2A1 gene (n = 9), and normal control mice (n = 11) were studied for skeletal abnormalities, using radiographic imaging and light microscopic analyses of histologic sections. The collagen network of cartilage was also investigated with transmission electron microscopy.

    RESULTS: At 2 months of age, all transgenic mice had dysplastic changes in their long bones, flattened vertebral bodies, and osteoarthritic changes in their joints. The intervertebral discs of the transgenic animals were degenerated, and their histologic structure was disturbed. The changes were more severe in mice with no murine Col2a1 allele.

    CONCLUSION: The human COL2A1 gene with the Arg519Cys mutation causes osteochondrodysplasia in mice, as it does in humans.

  • 220.
    Sandgren, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Andersson, Martin
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Radiation dosimetry of [Ga-68]PSMA-11 in low-risk prostate cancer patients2019In: EJNMMI Physics, ISSN 2197-7364, E-ISSN 2191-219X, Vol. 6, article id 2Article in journal (Refereed)
    Abstract [en]

    Background: 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ([68Ga]PSMA-11) has been increasingly used to image prostate cancer using positron emission tomography (PET)/computed tomography (CT) both during diagnosis and treatment planning. It has been shown to be of clinical value for patients both in the primary and secondary stages of prostate cancer. The aim of this study was to determine the effective dose and organ doses from injection of [68Ga]PSMA-11 in a cohort of low-risk prostate cancer patients.

    Methods: Six low-risk prostate cancer patients were injected with 133–178 MBq [68Ga]PSMA-11 and examined with four PET/CT acquisitions from injection to 255 min post-injection. Urine was collected up to 4 h post-injection, and venous blood samples were drawn at 45 min, 85 min, 175 min, and 245 min post-injection. Kidneys, liver, lungs, spleen, salivary and lacrimal glands, and total body where delineated, and cumulated activities and absorbed organ doses calculated. The software IDAC-Dose 2.1 was used to calculate absorbed organ doses according to the International Commission on Radiological Protection (ICRP) publication 107 using specific absorbed fractions published in ICRP 133 and effective dose according to ICRP Publication 103. We also estimated the absorbed dose to the eye lenses using Monte Carlo methods.

    Results: [68Ga]PSMA-11 was rapidly cleared from the blood and accumulated preferentially in the kidneys and the liver. The substance has a biological half-life in blood of 6.5 min (91%) and 4.4 h (9%). The effective dose was calculated to 0.022 mSv/MBq. The kidneys received approximately 40 mGy after an injection with 160 MBq [68Ga]PSMA-11 while the lacrimal glands obtained an absorbed dose of 0.12 mGy per administered MBq. Regarding the eye lenses, the absorbed dose was low (0.0051 mGy/MBq).

    Conclusion: The effective dose for [68Ga]PSMA-11 is 0.022 mSv/MBq, where the kidneys and lacrimal glands receiving the highest organ dose.

  • 221.
    Sandström, Agneta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Neurocognitive and endocrine dysfunction in women with exhaustion syndrome2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stress has emerged as one of the most important factors to consider in psychiatric diagnoses and has become a common reason for long-term sick leave (LTSL). Roughly 50% of LTSL due to psychiatric diseases are thought to be associated with work-related stress. The demarcation towards major depression is disputed, and no international consensus exists for how to diagnose and rehabilitate these individuals.

    The Swedish National Board of Health has suggested the term “exhaustion syndrome” to integrate these individuals into stress-related disorders. Prominent features of this syndrome are fatigue, sleeping disorders, and cognitive dysfunction. The cognitive dysfunction may be due to an interaction between personality features, environmental factors, the biological effects of stress hormones, and dysfunction in key brain areas, notably the hippocampus and prefrontal cortex. A consistent feature of chronic stress is activation of the cortisol, or hypothalamic-pituitary-adrenal, axis, which may be linked to cognitive dysfunction. Increased glucocorticoid levels, mainly cortisol in humans, are known to impair memory performance. The aim of this thesis was to investigate whether patients with exhaustion syndrome exhibit specific alterations in an extensive set of biological, psychological and immunological variables.

    Patients in Study 1 had significant cognitive impairment for specific tasks assumed to tap frontal lobe functioning. In Study 2 anxiety prone, worrying, pessimistic individuals with low executive drive and a persistent personality type were more likely to develop exhaustion syndrome. Decreased reactivity was found on the pituitary level after corticotropin releasing hormone (CRH) in exhaustion syndrome patients. The cortisol/adrenocorticotropic hormone response to CRH was slightly higher in patients compared to controls, indicating increased sensitivity at the adrenal cortex level. No differences were found in hippocampal volume. In Study 3, functional imaging revealed a different pattern of brain activation in working memory tests in patients with exhaustion syndrome compared to healthy individuals and patients with depression.

    In summary, our data suggests an intimate link between personality and wellbeing, cognitive performance and neuroendocrine dysfunction, in exhaustion syndrome. We thus find similarities with major depression but also distinct differences between the exhaustion syndrome and major depression.

  • 222.
    Sandström, Agneta
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Peterson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Erik
    Anesthesia and Intensive care, Östersund, Sweden.
    Lundberg, Mattias
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Rhodin Nyström, Ingalill
    Quranten Stress and Trauma Institute, Umeå, Sweden.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Cognitive deficits in relation to personality type and hypothalamic-pituitary-adrenal (HPA) axis dysfunction in women with stress-related exhaustion2011In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 52, no 1, p. 71-82Article in journal (Refereed)
    Abstract [en]

    Exhaustion caused by long-term work-related stress may cause cognitive dysfunction. We explored factors that may link chronic stress and cognitive impairment. Personality, psychiatric screening, and behavior were assessed by self-reporting measures in 20 female patients (mean age 39.3 years; range 26–53) with a preliminary diagnosis of stress-related exhaustion and in 16 healthy matched controls. Cognitive performance was investigated with a detailed neuropsychological test battery. Cortisol axis function was assessed by urinary and saliva collections of cortisol, dexamethasone suppression, Synacthen response, and corticotropin-releasing hormone (CRH) tests. Proinflammatory cytokines were measured. Hippocampal volumes were estimated by magnetic resonance imaging. Multivariate and univariate statistical methods were used to explore putative differences between groups and factors linked to cognitive impairment. Cognitive function clearly differed between groups, with decreased attention and visuospatial memory in the patient group, suggesting frontal cortex/medial temporal cortex-network dysfunction. Increased harm avoidance and persistence was present among patients, with lowered self-directedness linked to lower quality of life, increased anxious and depressive tendencies, and experiences of psychosocial stress. Attention was decreased with concomitantly impaired visuospatial memory. The pituitary (adrenocorticotropic hormone, ACTH) response to CRH was decreased in patients, with an increased cortisol/ACTH response to CRH. However, cortisol production rates, diurnal or dexamethasone-suppressed saliva cortisol levels, and the cortisol response to Synacthen were unaltered. Hippocampal volumes did not differ between groups. These findings suggest that cognitive dysfunction in stress-related exhaustion is linked to distinct personality traits, low quality of life, and a decreased ACTH response to CRH.

  • 223.
    Sandvig, Axel
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sandvig, Ioanna
    Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
    Berry, Martin
    Molecular Neuroscience, Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.
    Olsen, Oystein
    Department of Radiography, Sør-Trondelag University College, Trondheim, Norway.
    Pedersen, Tina Bugge
    Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
    Brekken, Christian
    Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
    Thuen, Marte
    Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
    Axonal tracing of the normal and regenerating visual pathway of mouse, rat, frog, and fish using manganese-enhanced MRI (MEMRI)2011In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 34, no 3, p. 670-675Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess optic nerve (ON) regeneration after injury by applying manganese-enhanced MRI (MEMRI) in a study of comparative physiology between nonregenerating rat and mouse species and regenerating frog and fish species.

    Materials and Methods: The normal visual projections of rats, mice, frogs, and fish was visualized by intravitreal MnCl(2) injection followed by MRI. Rats and mice with ON crush (ONC) were divided into nonregenerating (ONC only), and regenerating animals with peripheral nerve graft (ONC+PNG; rats) or lens injury (ONC+LI; mice) and monitored by MEMRI at 1 and 20 days post-lesion (dpl). Frog and fish with ON transection (ONT) were monitored by MEMRI up to 6 months postlesion (mpl).

    Results: Signal intensity profiles of the Mn(2+)-enhanced ON were consistent with ON regeneration in the ONC+PNG and ONC+LI rat and mice groups, respectively, compared with the nonregenerating ONC groups. Furthermore, signal intensity profiles of the Mn(2+)-enhanced ON obtained between 1 mpl and 6 mpl in the fish and frog groups, respectively, were consistent with spontaneous, complete ON regeneration.

    Conclusion: Taken together, these results demonstrate that MEMRI is a viable method for serial, in vivo monitoring of normal, induced, and spontaneously regenerating optic nerve axons in different species.

  • 224. Sandvig, Ioanna
    et al.
    Hoang, Linh
    Sardella, Thomas C. P.
    Barnett, Susan C.
    Brekken, Christian
    Tvedt, Kare
    Berry, Martin
    Haraldseth, Olav
    Sandvig, Axel
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Thuen, Marte
    Labelling of olfactory ensheathing cells with micron-sized particles of iron oxide and detection by MRI2012In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, Vol. 7, no 4, p. 403-410Article in journal (Refereed)
    Abstract [en]

    A crucial issue in transplant-mediated repair of the damaged central nervous system (CNS) is serial non-invasive imaging of the transplanted cells, which has led to interest in the application of magnetic resonance imaging (MRI) combined with designated intracellular magnetic labels for cell tracking. Micron-sized particles of iron oxide (MPIO) have been successfully used to track cells by MRI, yet there is relatively little known about either their suitability for efficient labelling of specific cell types, or their effects on cell viability. The purpose of this study was to develop a suitable MPIO labelling protocol for olfactory ensheathing cells (OECs), a type of glia used to promote the regeneration of CNS axons after transplantation into the injured CNS. Here, we demonstrate an OEC labelling efficiency of >90% with an MPIO incubation time as short as 6?h, enabling intracellular particle uptake for single-cell detection by MRI without affecting cell proliferation, migration and viability. Moreover, MPIO are resolvable in OECs transplanted into the vitreous body of adult rat eyes, providing the first detailed protocol for efficient and safe MPIO labelling of OECs for non-invasive MRI tracking of transplanted OECs in real time for use in studies of CNS repair and axon regeneration. Copyright (c) 2012 John Wiley & Sons, Ltd.

  • 225. Sandvig, Ioanna
    et al.
    Thuen, Marte
    Hoang, Linh
    Olsen, Oystein
    Sardella, Thomas C. P.
    Brekken, Christian
    Tvedt, Kare E.
    Barnett, Susan C.
    Haraldseth, Olav
    Berry, Martin
    Sandvig, Axel
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    In vivo MRI of olfactory ensheathing cell grafts and regenerating axons in transplant mediated repair of the adult rat optic nerve2012In: NMR in Biomedicine, ISSN 0952-3480, E-ISSN 1099-1492, Vol. 25, no 4, p. 620-631Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to use magnetic resonance imaging (MRI) as a tool for monitoring transplant-mediated repair of the adult rat visual pathway. We labelled rat olfactory ensheathing cells (OECs) using micron-sized particles of iron oxide (MPIO) and transplanted them by: i) intravitreal injection (ivit) and ii) intra-optic nerve (ON) injection (iON) in adult rats with ON crush (ONC) injury. We applied T2-weighted MRI and manganese-enhanced MRI (MEMRI) to visualise transplanted cells and ON axons at specific times after injury and cell engraftment. Our findings demonstrate that ivit MPIO-labelled OECs are unequivocally detected by T2-weighted MRI in vivo and that the T1-weighted 3D FLASH sequence applied for MEMRI facilitates simultaneous visualisation of Mn2+-enhanced regenerating retinal ganglion cell (RGC) axons and MPIO-labelled OEC grafts. Furthermore, analysis of MRI data and ultrastructural findings supports the hypothesis that iON OEC transplants mediate regeneration and remyelination of RGC axons post injury.

  • 226. Saran, F.
    et al.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Center Stockholm and Umeå University, Stockholm/Umeå.
    Mason, W.
    Wick, W.
    Nishikawa, R.
    Cloughesy, T.
    Hilton, M.
    Kerloeguen, Y.
    Chinot, O. L.
    The Addition of Bevacizumab (BEV) to Temozolomide (TMZ) and Radiation Therapy (RT) in Newly Diagnosed Glioblastoma (GBM) Improves Progression-Free Survival (PFS) Without Adding to RT Toxicity2013In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 87, no 2, Supplement S, p. S16-S16Article in journal (Other academic)
  • 227. Sardanelli, Francesco
    et al.
    Bashir, Humayun
    Berzaczy, Dominik
    Cannella, Guglielmo
    Espeland, Ansgar
    Flor, Nicola
    Helbich, Thomas
    Hunink, Myriam
    Malone, Dermot E.
    Mann, Ritse
    Muzzupappa, Claudia
    Petersen, Lars J.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sconfienza, Luca M.
    Serafin, Zbigniew
    Spronk, Sandra
    Stoker, Jaap
    Van Beek, Edwin J. R.
    Vorwerk, Dierk
    Di Leo, Giovanni
    The Role of Imaging Specialists as Authors of Systematic Reviews on Diagnostic and Interventional Imaging and Its Impact on Scientific Quality: Report from the EuroAIM Evidence-based Radiology Working Group2014In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 272, no 2, p. 533-540Article, review/survey (Refereed)
    Abstract [en]

    Purpose: To evaluate the inclusion of radiologists or nuclear medicine physicians (imaging specialists) as authors of systematic reviews (SRs) on imaging and imaging-guided diagnostic procedures and to determine the impact of imaging specialists' presence as authors on the overall quality of the reviews.

    Materials and Methods: A MEDLINE and EMBASE search was performed for SRs of diagnostic and interventional image-guided procedures that were published from January 2001 to December 2010. SRs about procedures primarily performed by nonimaging specialists were excluded. The inclusion of imaging specialists among the SR authors and the frequency of publication in imaging journals were evaluated. The quality of a subset of 200 SRs (100 most recent SRs with imaging specialists as authors and 100 most recent SRs without imaging specialists as authors) was rated by using a 12-item modified assessment of multiple SRs (AMSTAR) evaluation tool. Spearman, chi(2), and Mann-Whitney statistics were used.

    Results: From among 3258 retrieved citations, 867 SRs were included in the study. Neuroimaging had the largest number of SRs (28% [241 of 867]), 41% (354 of 867) of SRs concerned diagnostic performance, and 26% (228 of 867) of SRs were published in imaging journals. Imaging specialists were authors (in any position) in 330 (38%) of 867 SRs; they were first authors of 176 SRs and last authors of 161 SRs. SRs with imaging specialists as authors were more often published in imaging journals than in nonimaging journals (54% [179 of 330] vs 9% [49 of 537]; P < .001). The median number of modified AMSTAR quality indicators was nine in SRs with imaging specialists as authors, while that in SRs without imaging specialists as authors was seven (P = .003).

    Conclusion: Only 38% (330 of 867) of SRs on radiology or nuclear medicine-related imaging published from January 2001 to December 2010 included imaging specialists as authors. However, the inclusion of imaging specialists as authors was associated with a significant increase in the scientific quality (as judged by using a modified AMSTAR scale) of the SR. 

  • 228.
    Schrauben, Eric
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Wisconsin, USA.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Department of Radiology, University of Wisconsin – Madison, Madison, Wisconsin, USA.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Spaak, Erik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wieben, Oliver
    University of Wisconsin – Madison, Madison, Wisconsin, USA.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Fast 4D flow MRI intracranial segmentation and quantification in tortuous arteries2015In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 42, no 5, p. 1458-1464Article in journal (Refereed)
    Abstract [en]

    PurposeTo describe, validate, and implement a centerline processing scheme (CPS) for semiautomated segmentation and quantification in carotid siphons of healthy subjects. 4D flow MRI enables blood flow measurement in all major cerebral arteries with one scan. Clinical translational hurdles are time demanding postprocessing and user-dependence induced variability during analysis. Materials and MethodsA CPS for 4D flow data was developed to automatically separate cerebral artery trees. Flow parameters were quantified at planes along the centerline oriented perpendicular to the vessel path. At 3T, validation against 2D phase-contrast (PC) magnetic resonance imaging (MRI) and 4D flow manual processing was performed on an intracranial flow phantom for constant flow, while pulsatile flow validation was performed in the internal carotid artery (ICA) of 10 healthy volunteers. The CPS and 4D manual processing times were measured and compared. Flow and area measurements were also demonstrated along the length of the ICA siphon. ResultsPhantom measurements for area and flow were highly correlated between the CPS and 2D measurements (area: R=0.95, flow: R=0.94), while in vivo waveforms were highly correlated (R=0.93). Processing time was reduced by a factor of 4.6 compared with manual processing. Whole ICA measurements revealed a significantly decreased area in the most distal segment of the carotid siphon (P=0.0017), with flow unchanged (P=0.84). ConclusionThis study exhibits fast semiautomated analysis of intracranial 4D flow MRI. Internal consistency was shown through flow conservation along the tortuous ICA siphon, which is typically difficult to assess. J. Magn. Reson. Imaging 2015;42:1458-1464.

  • 229.
    Silvast, Tuomo
    et al.
    Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland; BioMater Center, University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Aula, Antti
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland; Department of Physics, University of Kuopio, Kuopio, Finland.
    Contrast agent-enhanced computed tomography of articular cartilage: association with tissue composition and properties.2009In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 50, no 1, p. 78-85, article id 19052932Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Contrast agent-enhanced computed tomography may enable the noninvasive quantification of glycosaminoglycan (GAG) content of articular cartilage. It has been reported that penetration of the negatively charged contrast agent ioxaglate (Hexabrix) increases significantly after enzymatic degradation of GAGs. However, it is not known whether spontaneous degradation of articular cartilage can be quantitatively detected with this technique.

    PURPOSE: To investigate the diagnostic potential of contrast agent-enhanced cartilage tomography (CECT) in quantification of GAG concentration in normal and spontaneously degenerated articular cartilage by means of clinical peripheral quantitative computed tomography (pQCT).

    MATERIAL AND METHODS: In this in vitro study, normal and spontaneously degenerated adult bovine cartilage (n=32) was used. Bovine patellar cartilage samples were immersed in 21 mM contrast agent (Hexabrix) solution for 24 hours at room temperature. After immersion, the samples were scanned with a clinical pQCT instrument. From pQCT images, the contrast agent concentration in superficial as well as in full-thickness cartilage was calculated. Histological and functional integrity of the samples was quantified with histochemical and mechanical reference measurements extracted from our earlier study.

    RESULTS: Full diffusion of contrast agent into the deep cartilage was found to take over 8 hours. As compared to normal cartilage, a significant increase (11%, P<0.05) in contrast agent concentration was seen in the superficial layer of spontaneously degenerated samples. Significant negative correlations were revealed between the contrast agent concentration and the superficial or full-thickness GAG content of tissue (|R| > 0.5, P<0.01). Further, pQCT could be used to measure the thickness of patellar cartilage.

    CONCLUSION: The present results suggest that CECT can be used to diagnose proteoglycan depletion in spontaneously degenerated articular cartilage with a clinical pQCT scanner. Possibly, the in vivo use of clinical pQCT for CECT arthrography of human joints is feasible.

  • 230.
    Silvast, Tuomo
    et al.
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Clinical Neurophysiology, Kuopio University Hospital and University of Kuopio, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
    Lammi, Mikko
    Department of Biomedicine, Anatomy, University of Kuopio, Kuopio, Finland; Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Töyräs, Juha
    Department of Physics, University of Kuopio, Kuopio, Finland; Department of Clinical Neurophysiology, Kuopio University Hospital and University of Kuopio, Kuopio, Finland.
    pQCT study on diffusion and equilibrium distribution of iodinated anionic contrast agent in human articular cartilage – associations to matrix composition and integrity.2009In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 17, no 1, p. 26-32, article id 18602844Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: X-ray imaging of articular cartilage using anionic contrast agents has been introduced for quantification of tissue glycosaminoglycan (GAG) concentration. In this in vitro study we investigated diffusion and equilibrium distribution of an anionic contrast agent in human articular cartilage and related the results to tissue composition and integrity.

    METHODS: Osteochondral cylinders (d=4.0mm, n=24) were prepared from femoral medial condyles (FMCs, cartilage thickness 2.13+/-0.54 mm, mean+/-standard deviation [SD]), and tibial medial plateaus ([TMPs]1.99+/-0.38 mm) of human cadaver knees. Samples were immersed for 24h at room temperature in 21 mM concentration of anionic contrast agent Hexabrix. The X-ray absorption maps and profiles were measured before immersion, and after every 2h of immersion using clinical peripheral quantitative computed tomography (pQCT).

    RESULTS: An increase in X-ray attenuation along cartilage depth, indicating a characteristic density profile increasing from superficial to deep tissue, could be seen in pQCT images acquired without contrast agent. The complete diffusion of the contrast agent into cartilage took more than 12h. However, the uronic acid concentration correlated with the contrast agent concentration in femoral cartilage (r=-0.76, n=12, P=0.004) as early as after 2h of immersion, and the linear correlation was virtually unchanged during the remaining 22 h. Similarly, the histological tissue integrity (Mankin score) correlated positively with the contrast agent concentration in tibial cartilage (r=+0.75, P=0.005) after 2h of immersion. The X-ray absorption profiles before immersion, i.e., without the contrast agent, and after 24h of immersion were significantly correlated (r=-0.76+/-0.34, mean+/-SD).

    CONCLUSIONS: Although the complete contrast agent diffusion into human articular cartilage in vitro took more than 12h, significant apparent correlations were revealed between the spatial proteoglycan (PG) and contrast agent distributions already after 2h of immersion. At the stage of incomplete penetration, however, the spatial contrast agent concentration distribution cannot directly reflect the true PG distribution as the Donnan equilibrium has not been reached. However, in degenerated cartilage the diffusion rate increases. Obviously, this can lead to the reported correlation between the bulk PG content and the bulk contrast agent concentration already at the early stages of diffusion.

  • 231. Sjöberg, Carl
    et al.
    Lundmark, Martin
    Granberg, Christoffer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Silvia
    Ahnesjo, Anders
    Montelius, Anders
    Clinical evaluation of multi-atlas based segmentation of lymph node regions in head and neck and prostate cancer patients2013In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 8, p. Article number: 229-Article in journal (Refereed)
    Abstract [en]

    Background: Semi-automated segmentation using deformable registration of selected atlas cases consisting of expert segmented patient images has been proposed to facilitate the delineation of lymph node regions for three-dimensional conformal and intensity-modulated radiotherapy planning of head and neck and prostate tumours. Our aim is to investigate if fusion of multiple atlases will lead to clinical workload reductions and more accurate segmentation proposals compared to the use of a single atlas segmentation, due to a more complete representation of the anatomical variations. Methods: Atlases for lymph node regions were constructed using 11 head and neck patients and 15 prostate patients based on published recommendations for segmentations. A commercial registration software (Velocity AI) was used to create individual segmentations through deformable registration. Ten head and neck patients, and ten prostate patients, all different from the atlas patients, were randomly chosen for the study from retrospective data. Each patient was first delineated three times, (a) manually by a radiation oncologist, (b) automatically using a single atlas segmentation proposal from a chosen atlas and (c) automatically by fusing the atlas proposals from all cases in the database using the probabilistic weighting fusion algorithm. In a subsequent step a radiation oncologist corrected the segmentation proposals achieved from step (b) and (c) without using the result from method (a) as reference. The time spent for editing the segmentations was recorded separately for each method and for each individual structure. Finally, the Dice Similarity Coefficient and the volume of the structures were used to evaluate the similarity between the structures delineated with the different methods. Results: For the single atlas method, the time reduction compared to manual segmentation was 29% and 23% for head and neck and pelvis lymph nodes, respectively, while editing the fused atlas proposal resulted in time reductions of 49% and 34%. The average volume of the fused atlas proposals was only 74% of the manual segmentation for the head and neck cases and 82% for the prostate cases due to a blurring effect from the fusion process. After editing of the proposals the resulting volume differences were no longer statistically significant, although a slight influence by the proposals could be noticed since the average edited volume was still slightly smaller than the manual segmentation, 9% and 5%, respectively. Conclusions: Segmentation based on fusion of multiple atlases reduces the time needed for delineation of lymph node regions compared to the use of a single atlas segmentation. Even though the time saving is large, the quality of the segmentation is maintained compared to manual segmentation.

  • 232.
    Sjögren, Adam
    Umeå University, Faculty of Science and Technology, Department of Physics.
    The impact of metallic cranial implants on proton-beam radiotherapy treatment plans for near implant located tumours: A phantom study on the physical effects and agreement between simulated treatment plans and the resulting treatment for near implant located cranial tumours2018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Within the field of radiotherapy treatments of tumour diseases, the hunt for more accurate and effective treatment methods is a continuous process. For some years ion-beam based radiotherapy, especially the proton-beam based applications, has increased in popularity and availability. The main reason behind this is the fact that ion-beam based applications make it possible to modulate the dose after the planning target volume (PTV) defined by the radiation oncologist. This means that it becomes possible to spare tissue in another way, which might result in more effective treatments, especially in the vicinity of radio sensitive organs. Ion-beam based treatments are however more sensitive to uncertainties in PTV position and beam range as ion-beams have a fixed range depending on target media and initial energy, as opposed to the conventional x-ray beams that do not really have a defined range. Instead their intensity decreases exponentially at a rate dependent of the initial energy and target media. Therefore density heterogeneities result in uncertainties in the planned treatments. As the plans normally are created using a CT-images, for which metallic implants can yield increased heterogeneities both from the implants themselves and so called metal artifacts (distortions in the images caused by different processes as the X-rays used in image acquisition goes through metals). Metallic implants affects the accuracy of a treatment, and therefore also the related risks, so it is important to have an idea of the magnitude of the impact. Therefore the aim of this study is to estimate the impact on a proton-beam based treatment plan for six cranial implants. These were one Ti-mesh implant, one temporal plate implant, one burr-hole cover implant and three craniofix implants of different sizes, which all are commonly seen at the Skandion clinic. Also the ability of the treatment planning system (TPS), used at the clinic, to simulate the effects on the plans caused by the implants is to be studied. From this result it should be estimated if the margins and practices in place at the clinic, for when it is required to aim the beam through the implant, are sufficient or if they should be changed.

    This study consisted of one test on the range shift effects and one test on the lateral dose distribution changes, with one preparational test in the form of a calibration of Gafchromic EBT3 films. The range shift test was performed on three of the implants, excluding the three craniofix implants using a water phantom and a treatment plan created to represent a standard treatment in the cranial area. The lateral dose distribution change test was performed as a solid phantom study using radiochromic film, for two treatment plans (one where the PTV was located \SI{2}{\centi\metre} below surface, for all implants, and one where it was located at the surface, only for the Ti-mesh and the temporal plate). The results of both tests were compared to simulations performed in the Eclipse treatment planing system (TPS) available at Skandion.

    The result of the range shift test showed a maximum range shift of \SI{-1.03 +- 0.01}{\milli\metre}, for the burr-hole cover implant, and as the related Eclipse simulations showed a maximal shift of \SI{-0.17 +- 0.01}{\milli\metre} there was a clear problem with the simulation. However, this might not be because of the TPS but due to errors in the CT-image reconstruction, such as, for example, geometrical errors in the representation of the implants. As the margin applied for a similar situation at the Skandion clinic (in order to correct for several uncertainty factors) is \SI{4.2}{\milli\metre} there might be a need to increase this margin depending on the situation.

    For the lateral distribution effects no definite results were found as the change varied in magnitude, even if it tended to manifest as a decreasing dose for the first plan and a increasing dose for the second. It was therefore concluded that further studies are needed before anything clear can be said.

  • 233.
    Skorpil, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Department of Radiology, Uppsala University Hospital, Uppsala, Sweden.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Engström, M.
    Motion corrected DWI with integrated T2-mapping for simultaneous estimation of ADC, T2-relaxation and perfusion in prostate cancer2017In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 39, p. 162-167Article in journal (Refereed)
    Abstract [en]

    Objective: Multiparametric magnetic resonance imaging (MRI) and PI-RADS (Prostate Imaging - Reporting and Data System) has become the standard to determine a probability score for a lesion being a clinically significant prostate cancer. T2-weighted and diffusion-weighted imaging (DWI) are essential in PI-RADS, depending partly on visual assessment of signal intensity, while dynamic-contrast enhanced imaging is less important. To decrease inter-rater variability and further standardize image evaluation, complementary objective measures are in need. Methods: We here demonstrate a sequence enabling simultaneous quantification of apparent diffusion coefficient (ADC) and T2-relaxation, as well as calculation of the perfusion fraction f from low b-value intravoxel incoherent motion data. Expandable wait pulses were added to a FOCUS DW SE-EPI sequence, allowing the effective echo time to change at run time. To calculate both ADC and f, b-values 200 s/mm(2) and 600 s/mm(2) were chosen, and for T2-estimation 6 echo times between 64.9 ms and 114.9 ms were used. Results: Three patients with prostate cancer were examined and all had significantly decreased ADC and T2 values, while f was significantly increased in 2 of 3 tumors. T2 maps obtained in phantom measurements and in a healthy volunteer were compared to T2 maps from a SE sequence with consecutive scans, showing good agreement. In addition, a motion correction procedure was implemented to reduce the effects of prostate motion, which improved T2-estimation. Conclusions: This sequence could potentially enable more objective tumor grading, and decrease the inter-rater variability in the PI-RADS classification.

  • 234.
    Skorpil, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Department of Radiology, Uppsala, Sweden.
    Rydén, Henric
    Wejde, Johan
    Lidbrink, Elisabet
    Brosjo, Otte
    Berglund, Johan
    The effect of radiotherapy on fat content and fatty acids in myxoid liposarcomas quantified by MRI2017In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 43, p. 37-41Article in journal (Refereed)
    Abstract [en]

    Background: Myxoid liposarcomas are highly radiosensitive. Consequently radiotherapy is often used pre-operatively to reduce tumor volume and lessen the post-operative deficit. In soft-tissue sarcomas therapy response is mainly evaluated using magnetic resonance imaging (MRI) and the fundamental criterion for a positive response is decreased tumor size. In myxoid liposarcomas an increased fat content is also known to occur as a response to radiotherapy. Objective: To highlight the difficulties of MRI for therapy response evaluation in irradiated myxoid liposarcomas, by using MRI Dixon techniques enabling objective quantification of proton density fat fraction (%) and the number of double bonds (ndb; unsaturation degree) of fatty acids. Secondly, to compare quantitative fat fraction measurements versus visual grading of fat content on T1-weighted images. Case descriptions: Prior to surgery, two patients with myxoid liposarcoma were treated with 50 Gy. Following radiotherapy, both tumors on MRI showed reduced size, elevated fat fraction and transformed fat fraction histograms with diverse changes of ndb, while histopathological specimens showed discordant treatment effects; one case having good response and the other having poor response. Conclusions: A decrease in tumor size and increase in fat content on MRI cannot be interpreted as positive therapy response in radiotherapy of myxoid liposarcomas. Our data also give further supporting evidence that differentiation and maturation of tumor cells is the cause for the lipoma-like areas seen after radiotherapy. Finally, quantitative MRI Dixon techniques are preferable to visual grading for estimating the fat content in lipomatous tumors.

  • 235. Sneve, Markus H.
    et al.
    Grydeland, Hakon
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bowles, Ben
    Amlien, Inge K.
    Langnes, Espen
    Walhovd, Kristine B.
    Fjell, Anders M.
    Mechanisms Underlying Encoding of Short-Lived Versus Durable Episodic Memories2015In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, no 13, p. 5202-5212Article in journal (Refereed)
    Abstract [en]

    We continuously encounter and process novel events in the surrounding world, but only some episodes will leave detailed memory traces that can be recollected after weeks and months. Here, our aim was to monitor brain activity during encoding of events that eventually transforms into long-term stable memories. Previous functional magnetic resonance imaging (fMRI) studies have shown that the degree of activation of different brain regions during encoding is predictive of later recollection success. However, most of these studies tested participants' memories the same day as encoding occurred, whereas several lines of research suggest that extended post-encoding processing is of crucial importance for long-term consolidation. Using fMRI, we tested whether the same encoding mechanisms are predictive of recollection success after hours as after a retention interval of several weeks. Seventy-eight participants were scanned during an associative encoding task and given a source memory test the same day or after similar to 6 weeks. We found a strong link between regional activity levels during encoding and recollection success over short time intervals. However, results further showed that durable source memories, i.e., events recollected after several weeks, were not simply the events associated with the highest activity levels at encoding. Rather, strong levels of connectivity between the right hippocampus and perceptual areas, as well as with parts of the self-referential default-mode network, seemed instrumental in establishing durable source memories. Thus, we argue that an initial intensity-based encoding is necessary for short-term encoding of events, whereas additional processes involving hippocampal-cortical communication aid transformation into stable long-term memories.

  • 236.
    Stenholm, Natalie
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    What differences are there between community hospitals and general hospitals? - A study on care interventions and the documentation in the medical records.2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 237.
    Stenman, Katarina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Prostate Cancer Diagnosis: experimental and Clinical Studies With HRMAS NMR Spectroscopy2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A few abnormal cells found in a small piece of prostate tissue are most consequential for a man’s future.

    The prevalence of prostate cancer (PCa) is increasing globally. The main instigating factor for this cancer is not yet known, but it appears to be the consequence of many variables such as an increasingly older population, more frequent PSA-testing, and factors involving lifestyle.

    Prostate cancer screening, as an equivalent for breast cancer screening, has been suggested but unfortunately there are no accurate diagnostic tools available for this type of screening. The reason for this is simply that the prostate is one of the most difficult organs to diagnose and, consequently, PCa screening would generate far too many false-positive and false-negative results.  The prostate is not easily accessible as it is deeply-seated in the male pelvic area, wrapped around the urethra and surrounded by sensitive vital organs.  Furthermore, PCa is frequently multi-focal, and the cancer cells have a tendency of assimilating among normal cells and, thus, do not always form solid lumps.  Therefore, prostate tumors are often not felt by digital rectal examination (DRE) or identified by imaging.  The PSA-test is not reliable as it is more prostate-specific than cancer-specific.  Due to increasing prostate awareness, more early-stage and locally confined PCa are being detected. This is saving lives, although there is a high risk of over treatment and unnecessary side-effects.  The increased detection of PCa requires sophisticated diagnostic methods and highly skilled clinicians who can discern between indolent and aggressive cancers.  The current “gold-standard” for PCa diagnosis is biopsy grading by pathologists using the Gleason score system, which is a difficult task.  Therefore, innovative methods to improve the precision of prostate diagnosis, by increased biopsy sensitivity and tumor localization, are of essence.

    In light of these difficulties, the metabolomic approach using 1D and 2D high-resolution magic angle spinning (HRMAS) NMR spectroscopy combined with histopathology on intact prostatectomy specimens was evaluated in this research project.  The non-destructive nature of HRMAS NMR enables spectroscopic analysis of intact tissue samples with consecutive histological examinations under light microscope. Metabolomics aids in the unraveling and the discovery of organ-specific endogenous metabolites that have the potential to be reliable indicators of organ function and viability, extrinsic and intrinsic perturbations, as well as valuable markers for treatment response. The results may, therefore, be applied clinically to characterize an organ by utilizing biomarkers that have the capacity to distinguish between disease and health.

    The aim was to characterize the human and the rat prostate in terms of its intermediary metabolism, which I show here to differ between species and anatomical regions.  Furthermore, the aim is to seek the verification of HRMAS NMR derived metabolites which are known to be a part of the prostate metabolome such as, citrate, choline, and the polyamines which were performed, but also the identification of metabolites not previously identified as part of the local prostate metabolism, such as Omega-6, which was detected in tumors.  The extended aim was to elucidate novel bio-markers with clinical potential. In this study, the common phyto-nutrient, inositol, which appears to possess protective properties, was identified as being a potentially important PCa bio-marker for the distinction between the more indolent Gleason score 6 and the more aggressive Gleason score 7 in non-malignant prostate tissues with tumors elsewhere in the organ. Further studies in this area of PCa research are therefore warranted.

  • 238. Stensdotter, A.
    et al.
    Pedersen, N.
    Wanvik, A.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Flovig, J. C.
    Fors, E. A.
    Upper body 3-dimensional kinematics during gait in psychotic patients: a pilot-study2012In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 221, no 4, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Gait is recognized as a key item related to mental function. Anomalous gait in psychotic individuals has been described for the lower extremities, whereas irregularities for upper body dynamics are not described, explained or verified with unbiased methods. Reduced walking velocity and increased somatic tension defined in this patient category may influence upper body dynamics during gait. The aim of this pilot-study was to describe upper body kinematics and investigate the biomechanical association with walking velocity and muscle tension. Twelve inpatients in a psychiatric ward with first-episode psychosis and 18 healthy control subjects walked at different self-chosen velocities. Movement and walking velocity were registered, and 3D kinematics was analysed for thorax and shoulder joint. Time-synchronized EMG from the trapezius muscle, chosen as indicator for general somatic tension, was analysed for maximal amplitude and variability. Results showed that patients walked with reduced arm swing at the shoulder joint and increased lateral thorax movements. Thorax rotations about the vertical axis, walking velocity and EMG measures were similar in patients and healthy subjects. The present study could not provide a biomechanical explanation for kinematic findings based on walking velocity or somatic tension.

  • 239. Stephensen, H
    et al.
    Andersson, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Tisell, M
    Wikkelsö, C
    Objective B wave analysis in 55 patients with non-communicating and communicating hydrocephalus2005In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, p. 965-970Article in journal (Refereed)
    Abstract [en]

    Background: B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH).

    Object: To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves.

    Methods: ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs.

    Results: There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients.

    Conclusions: B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

  • 240.
    Stoverud, Karen-Helene
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Center for Biomedical Computing, Simula Research Laboratory and Department of Informatics, University of Oslo, Oslo, Norway.
    Langtangen, Hans Petter
    Ringstad, Geir Andre
    Eide, Per Kristian
    Mardal, Kent-Andre
    Computational Investigation of Cerebrospinal Fluid Dynamics in the Posterior Cranial Fossa and Cervical Subarachnoid Space in Patients with Chiari I Malformation2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, article id e0162938Article in journal (Refereed)
    Abstract [en]

    Purpose Previous computational fluid dynamics (CFD) studies have demonstrated that the Chiari malformation is associated with abnormal cerebrospinal fluid (CSF) flow in the cervical part of the subarachnoid space (SAS), but the flow in the SAS of the posterior cranial fossa has received little attention. This study extends previous modelling efforts by including the cerebellomedullary cistern, pontine cistern, and 4th ventricle in addition to the cervical subarachnoid space. Methods The study included one healthy control, Con1, and two patients with Chiari I malformation, P1 and P2. Meshes were constructed by segmenting images obtained from T2-weighted turbo spin-echo sequences. CFD simulations were performed with a previously verified and validated code. Patient-specific flow conditions in the aqueduct and the cervical SAS were used. Two patients with the Chiari malformation and one control were modelled. Results The results demonstrated increased maximal flow velocities in the Chiari patients, ranging from factor 5 in P1 to 14.8 in P2, when compared to Con1 at the level of Foramen Magnum (FM). Maximal velocities in the cervical SAS varied by a factor 2.3, while the maximal flow in the aqueduct varied by a factor 3.5. The pressure drop from the pontine cistern to the cervical SAS was similar in Con1 and P1, but a factor two higher in P2. The pressure drop between the aqueduct and the cervical SAS varied by a factor 9.4 where P1 was the one with the lowest pressure jump and P2 and Con1 differed only by a factor 1.6. Conclusion This pilot study demonstrates that including the posterior cranial fossa is feasible and suggests that previously found flow differences between Chiari I patients and healthy individuals in the cervical SAS may be present also in the SAS of the posterior cranial fossa.

  • 241.
    Strandberg, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Hashemi, Armin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Optimization of PET reconstruction algorithm, SUV thresholding algorithm and PET acquisition time in clinical 11C-acetate PET/CT2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0209169Article in journal (Refereed)
    Abstract [en]

    Introduction 11C-acetate (ACE)-PET/CT is used for staging of high-risk prostate cancer. PET data is reconstructed with iterative algorithms, such as VUEPointHD ViP (VPHD) and VUEPoint HD Sharp IR (SharpIR), the latter with additional resolution recovery. It is expected that the resolution recovery algorithm should render more accurate maximum and mean standardized uptake values (SUVmax and SUVmean) and functional tumor volumes (FTV) than the ordinary OSEM. Performing quantitative analysis, choice of volume-of-interest delineation algorithm (SUV threshold) may influence FTV. Optimizing PET acquisition time is justified if image quality and quantitation do not deteriorate. The aim of this study is to identify the optimal reconstruction algorithm, SUV threshold and acquisition time for ACE-PET/CT. Methods ACE-PET/CT data acquired with a General Electric Discovery 690 PET/CT from 16 consecutive high-risk prostate cancer patients was reconstructed with VPHD and SharpIR. Forty pelvic lymph nodes (LNs) and 14 prostate glands were delineated with 42% and estimated threshold. SUVmax, SUVmean, FTV and total lesion uptake were measured. Default acquisition time was four minutes per bed position. In a subset of lesions, acquisition times of one, two and four minutes were evaluated. Structural tumor volumes (STV) of the LNs were measured with CT for correlation with functional volumetric parameters. To validate SUV quantification under different conditions with SharpIR 42%, recovery coefficients (RCs) of SUVmean and FTV were calculated from a phantom with 18F-fluoro-deoxy-glucose (FDG)-filled volumes 0.1–9.2cm3 and signal-to-background (S/B) ratios 4.3–15.9. Results With SharpIR, SUVmax and SUVmean were higher and FTV lower compared with VPHD, regardless of threshold method, in both prostates and LNs. Total lesion uptake determined with both threshold methods was lower with SharpIR compared with VPHD with both threshold methods, except in subgroup analysis of prostate targets where estimated threshold returned higher values. Longer acquisition times returned higher FTV for both threshold methods, regardless of reconstruction algorithm. The FTV difference was most pronounced with one minute’s acquisition per bed position, which also produced visually the highest noise. SUV parameters were unaffected by varying acquisition times. FTV with SharpIR 42% showed the best correspondence with STV. SharpIR 42% gave higher RCs of SUVmean and FTV with increasing phantom size and S/B-ratio, as expected. Conclusions Delineation with SharpIR 42% seems to provide the most accurate combined information from SUVmax, SUVmean, FTV and total lesion uptake. Acquisition time may be shortened to two minutes per bed position with preserved image quality.

  • 242.
    Strandberg, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, Camilla Thellenberg
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ögren, Mattias
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    11C-acetate PET/CT in pre-therapeutic lymph node staging in high-risk prostate cancer patients and its influence on disease management: a retrospective study2014In: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 4, no 55, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Background: Radiation treatment with simultaneous integrated boost against suspected lymph node metastases may be a curative therapeutic option in patients with high-risk prostate cancer (> 15% estimated risk of pelvic lymph node metastases according to the Cagiannos nomogram). C-11-acetate positron emission tomography/computed tomography (PET/CT) can be used for primary staging as well as for detection of suspected relapse of prostate cancer. The aims of this study were to evaluate the association between positive C-11-acetate PET/CT findings and the estimated risk of pelvic lymph node metastases and to assess the impact of C-11-acetate PET/CT on patient management in high-risk prostate cancer patients. Methods: Fifty consecutive prostate cancer patients referred for primary staging with C-11-acetate PET/CT prior to radiotherapy with curative intention were enrolled in this retrospective study. Results: All patients showed increased C-11-acetate uptake in the prostate. Pelvic lymph node uptake was seen in 42% (21/50) of the patients, with positive external iliac lymph nodes in 71% (15/21) of these. The overall observed proportion of PET/CT-positive pelvic lymph nodes at patient level was higher than the average estimated risk, especially in low-risk groups (< 15%). There was a significant association between observed proportion and estimated risk of pelvic lymph node metastases in groups with <= 45 and >45% estimated risk. Treatment strategy was altered due to C-11-acetate PET/CT findings in 43% (20/47) of the patients. Conclusions: The observed proportion of C-11-acetate PET/CT findings suggestive of locoregional metastases was higher than the estimated risk, suggesting that the Cagiannos nomogram underestimates the risk for metastases. The imaging results with C-11-acetate PET/CT have a considerable impact on patient management.

  • 243.
    Strengbom, Rebecca
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Evaluation of Growth Patterns of Colorectal Liver Metastases  Using 18F-Fluorodeoxyglucose and 15O-water Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 244.
    Sundström, Nina
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Andersson, Kennet
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Marmarou, Anthony
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Comparison between 3 infusion methods to measure cerebrospinal fluid outflow conductance2010In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 113, no 6, p. 1294-1303Article in journal (Refereed)
    Abstract [en]

    Object There are several infusion methods available to estimate the outflow conductance (Cout) or outflow resistance (Rout = 1/Cout) of the CSF system. It has been stated that for unknown reasons, the bolus infusion method estimates a higher Cout than steady-state infusion methods. The aim of this study was to compare different infusion methods for estimation of Cout.

    Methods The following 3 different infusion methods were used: the bolus infusion method (Cout bol); the constant flow infusion method, both static (Cout stat) and dynamic (Cout dyn) analyses; and the constant pressure infusion method (Cout cpi). Repeated investigations were performed on an experimental model with well-known characteristics, with and without physiological pressure variations (B-waves, breathing, and so on). All 3 methods were also performed in a randomized order during the same investigation in 20 patients with probable or possible idiopathic normal-pressure hydrocephalus; 6 of these patients had a shunt and 14 did not.

    Results Without the presence of physiological pressure variations, the concordance in the experimental model was good between all methods. When they were added, the repeatability was better for the steady-state methods and a significantly higher Cout was found with the bolus method in the region of clinically relevant Cout (p < 0.05). The visual fit for the bolus infusion was dependent on subjective assessment by the operator. This experimental finding was confirmed by the clinical results, where significant differences were found in the investigations in patients without shunts between Cout of the visual bolus method and Cout stat, Cout dyn, and Cout cpi (4.58, 4.18, and 6.12 μl/[second × kPa], respectively).

    Conclusions This study emphasized the necessity for standardization of Cout measurements. An experienced operator could partly compensate for difficulties in correctly estimating the pressure parameters for the bolus infusion method, but for the general user this study suggests a steady-state method for estimating Cout.

  • 245.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Human brain function evaluated with rCBF-SPECT: memory and pain related changes and new diagnostic possibilities in Alzheimer’s disease2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this doctoral thesis was to study the influence of memory, pain, age and education on the regional cerebral blood flow (rCBF), i.e. brain function, in early Alzheimer's disease (AD) and in chronic neck pain patients in comparison to healthy controls and in healthy elderly per se. This was done by optimizing single photon emission computed tomography (SPECT) as a method to study rCBF with the tracer Technetium-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO) and by matching all image data to a brain atlas before evaluation. The rCBF-SPECT was evaluated and developed to obtain higher diagnostic accuracy in AD and in chronic neck pain patients it was used to study basic pain related cerebral processes in chronic pain of different origin. A new semimanual registration method, based on fiducial marker, suitable for investigations with low spatial resolution was developed. The method was used to reconstruct images with an improved attenuation and scatter correction by using an attenuation-map calculated from the patients' previously acquired CT images.

    The influence of age and education on rCBF was evaluated with statistical parametric mapping, SPM in healthy elderly. The main findings were age related changes in rCBF in regions close to interlobar and interhemispheric space but not in regions typically affected in early AD, except for the medial temporal lobe. The theory of a 'cognitive reserve' in individuals with a longer education was supported with findings in the lateral temporal lobe, a region related to semantic memory, and in the frontal lobe.

    A cross-sectional study of chronic neck pain patients showed extensive rCBF changes in coping related regions in a non-traumatic pain patients compared to both healthy and a pain group with a traumatic origin, i.e. whiplash syndrome. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. This suggests different pain mechanisms in these groups.

    The AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus. These changes were associated to episodic memory performance, and especially to face recognition. The diagnostic sensitivity for AD was high. The face recognition test (episodic memory) was used in AD patients to improve the sensitivity of method, i.e. memory-provoked rCBF-SPECT (MP-SPECT). The results were compared to healthy controls and the reductions of rCBF in temporoparietal regions were more pronounced in mild AD during provocation. Memory provocation increased the sensitivity of AD-related rCBF changes at group level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might then be of help to set diagnosis earlier.

    In conclusion rCBF in temporoparietal regions are associated to an impaired episodic memory in early AD. Changes in these regions do not have a strong connection to chronological age. The diagnostic sensitivity of rCBF-SPECT in AD is high and there is a potentially higher sensitivity if memory provoked investigations are used. The findings in this thesis have given an increased knowledge of underlying cerebral pain processing in non-traumatic and traumatic (whiplash) neck pain. Preliminary results supporting the theory of 'cognitive reserve' by showing a correlation between long education and preserved rCBF was found in healthy elderly.

  • 246. Sydoff, Marie
    et al.
    Lizana, Helena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Mattsson, Soren
    Stabin, Michael G.
    Leide-Svegborn, Sigrid
    Determination of the biodistribution and dosimetry of I-123-FP-CIT in male patients with suspected Parkinsonism or Lewy body dementia using planar and combined planar and SPECT/CT imaging2013In: Applied Radiation and Isotopes, ISSN 0969-8043, E-ISSN 1872-9800, Vol. 82, p. 300-307Article in journal (Refereed)
    Abstract [en]

    In this study, I-123-FP-CIT biodistribution and dosimetry was determined in 10 adult male patients using planar gamma camera imaging alone or in combination with single photon emission computed tomography /X-ray computed tomography (SPECT/CT) imaging. Dosimetric assessment using planar plus SPECT/CT imaging resulted in significantly different estimates of organ-absorbed doses compared to estimates based on planar imaging alone. We conclude that the use of complementary SPECT/CT measurements in biodistribution studies is valuable for determining the organ doses more accurately.

  • 247.
    Söderlund, Sarah
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lundmark, Tommy
    Umeå University, Faculty of Medicine, Department of Nursing.
    Strålskydd för barn vid konventionell röntgen: En litteraturstudie2014Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Research shows that children are more sensitive to ionizing radiation than adults. X-ray imaging may not be performed unnecessarily and its necessity must exceed the risks. It is important to optimize the imaging and as far as possible minimize the radiation dose without affecting the diagnostic performance negatively. Research shows that even low doses of radiation can cause DNA damage and ultimately induce cancer. Objective: The aim of this paper was to describe methods that optimize the x-ray examination and reduce radiation doses to children in conventional radiography. Method: A literature study whose results are based on 14 scientific articles found in the databases PubMed and CINAHL and manual searches. Results: There were several methods that optimize the x-ray examination and reduce the radiation doses to children in conventional radiography. These methods concern approaches in the examination room, parameters, filtering and new technology. Conclusion: Radiographers’ with knowledge of optimization have good opportunities to lower radiation doses in x-ray examinations of children in conventional radiography.

  • 248. Tian, X.
    et al.
    Segars, P.
    Andersson, Jonas
    Umeå University.
    Pavlicek, W.
    Samei, E.
    A Reference Organ Dose Database for Body CT Examination Based On AAPM 2462015In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 42, no 6, p. 3746-3746Article in journal (Other academic)
  • 249.
    Toma-Dasu, Iuliana
    Umeå University, Faculty of Medicine, Radiation Sciences.
    Theoretical modelling of tumour oxygenation and influences on treatment outcome2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    One of the main problems in curing cancer resides in the different microenvironment existing in tumours compared to the normal tissues. The mechanisms of failure are different for radiotherapy and chemotherapy, but they all relate to the poor blood supply known to exist in tumours. It is therefore very important to know the tumour microenvironmental conditions in order to devise techniques that will overcome the problems and will therefore improve the result of the treatment.

    The aims of the thesis were the modelling of tumour oxygenation and the simulation of polarographic oxygen measurements in order to assess and possibly to improve the accuracy of the electrode in measuring tumour oxygenation. It also aimed to evaluate the implications of tumour microenvironment for the radiotherapy outcome.

    The project used theoretical modelling as the main tool. The processes of oxygen diffusion and consumption were described mathematically for different conditions, the result being very accurate distributions of oxygen in tissues. A first simple model of tissue oxygenation was based on the oxygen diffusion around a single blood vessel. A more complex model built from the basic physical processes and measurable parameters allowed the simulation of realistical tissues with heterogeneous vasculature. This model also allowed the modelling of the two types of hypoxia known to appear in tumours and their influence on the tumour microenvironment. The computer simulation of tissues was also used for assessing the accuracy of the polarographic technique for measuring tumour oxygenation.

    The results of this study have shown that it is possible to model theoretically the tissue oxygenation starting from the basic physical processes. The particular application of our theoretical simulation to the polarographic oxygen electrode has shown that this experimental method does not give the oxygen values in individual cells. Because the electrode measures the average oxygenation in a relatively large tissue volume, the resulting oxygen distributions are different from the real ones and the extreme high and low values are not detected. It has further been found that the polarographic electrode cannot make distinction between various types of hypoxia existing in tumours, the geometrical distribution of the hypoxic cells influencing mostly the accuracy of the measurement.

    It was also shown that because of the averaging implied by the measurement process, electrode results should not be used directly to predict the response to radiation. Thus, the differences between the predictions in clinical tumour control obtained from the real or the measured oxygenations are of the order of tens of percents in absolute value. A method to improve the accuracy of the electrode, i.e. to improve the correlation between the results of the measurements and the actual tissue oxygenation, was proposed.

    In conclusion, theoretical modelling has been shown to be a very powerful tool for predicting the outcome of radiotherapy and it has the advantage of describing the tumour oxygenation in the least invasive manner. Furthermore it allows the investigation of the invasiveness and the accuracy of various experimental methods.

  • 250.
    Trulsson, M
    et al.
    Karolinska Institute.
    Francis, S T
    University of Nottingham.
    Kelly, E F
    University of North Carolina.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bowtell, R
    University of Nottingham.
    McGlone, F
    Port Sunlight Laboratory, Unilever Research, Wirral, University of Wales, Bangor, United Kingdom, .
    Cortical responses to single mechanoreceptive afferent microstimulation revealed with fMRI2001In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 13, no 4, p. 613-622Article in journal (Refereed)
    Abstract [en]

    The technique of intraneural microneurography/microstimulation has been used extensively to study contributions of single, physiologically characterized mechanoreceptive afferents (MRAs) to properties of somatosensory experience in awake human subjects. Its power as a tool for sensory neurophysiology can be greatly enhanced, however, by combining it with functional neuroimaging techniques that permit simultaneous measurement of the associated CNS responses. Here we report its successful adaptation to the environment of a high-field MR scanner. Eight median-nerve MRAs were isolated and characterized in three subjects and microstimulated in conjunction with fMRI at 3.0 T. Hemodynamic responses were observed in every case, and these responses were robust, focal, and physiologically orderly. The combination of fMRI with microstimulation will enable more detailed studies of the representation of the body surface in human somatosensory cortex and further studies of the relationship of that organization to short-term plasticity in the human SI cortical response to natural tactile stimuli. It can also be used to study many additional topics in sensory neurophysiology, such as CNS responses to additional classes of afferents and the effects of stimulus patterning and unimodal/crossmodal attentional manipulations. Finally, it presents unique opportunities to investigate the basic physiology of the BOLD effect and to compare the operating characteristics of fMRI and EEG as human functional neuroimaging modalities in an unusually specific and well-characterized neurophysiological setting.

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